This laboratory is engaged in studies on protein structure and function. Specific questions include how a protein chain, which is synthesized as a random coil can fold to a highly specific secondary and tertiary structure without aid from any external agents. The blueprint for these higher order structures must be encoded in the proteins primary sequence. This mechanism of protein folding is being investigated by studies on the behavior of swine pepsinogen, studying the kinetics of its folding and unfolding reactions and the structure of partially folded intermediates observed in these reactions. Enzymic activity in folded proteins can be modulated or even totally suppressed by covalent modifications to the proteins structure. Two examples under investigation include activation of pepsinogen to the active enzyme pepsin, by cleavage of the polypeptide chain and modulation of the various activities of myosin by phosphorylation of both its heavy and light chains by a number of kinases, which are themselves under metabolic control. The sites of these reactions and their consequences are being studied.